The ever-growing world of gastruloids: autogenous models of mammalian embryogenesis.

During early development, extrinsic cues prompt a collection of pluripotent cells to begin the extensive process of cellular differentiation that gives rise to all tissues in the mammalian embryo, a process known as gastrulation. Advances in stem cell biology have resulted in the generation of stem cell-based in vitro models of mammalian gastrulation called gastruloids. Gastruloids and subsequent gastruloid-based models are tractable, scalable and more accessible than mammalian embryos. As such, they have opened an unprecedented avenue for modelling in vitro self-organisation, patterning and fate specification. This review focuses on discussing the recent advances of this rapidly moving research area, clarifying what structures they model and the underlying signal hierarchy. We highlight the exciting potential of these models and where the field might be heading.

An atlas of human kinase regulation.

The coordinated regulation of protein kinases is a rapid mechanism that integrates diverse cues and swiftly determines appropriate cellular responses. However, our understanding of cellular decision-making has been limited by the small number of simultaneously monitored phospho-regulatory events. Here, we have estimated changes in activity in 215 human kinases in 399 conditions derived from a large compilation of phosphopeptide quantifications. This atlas identifies commonly regulated kinases as those that are central in the signaling network and defines the logic relationships between kinase pairs. Co-regulation along the conditions predicts kinase-complex and kinase-substrate associations. Additionally, the kinase regulation profile acts as a molecular fingerprint to identify related and opposing signaling states. Using this atlas, we identified essential mediators of stem cell differentiation, modulators of Salmonella infection, and new targets of AKT1. This provides a global view of human phosphorylation-based signaling and the necessary context to better understand kinase-driven decision-making.